The Tobacco Smoke Constituent Biomarker Core will quantify urinary biomarkers of exposure to and metabolism of tobacco smoke toxicants and carcinogens. Total nicotine equivalents in urine will be quantified by measuring nicotine and its metabolites nicotine-/V-glucuronide, cotinine, cotinlne-/V-glucuronide, and trans-3'-hydroxycotinine and its glucuronides. Exposure to the tobacco-specific lung carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) will be assessed by quantitation of its urinary metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides. Exposure to and metabolism ofthe representative polycyclic aromatic hydrocarbon phenanthrene will be measured by quantifying Its metabolites f-1,/-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and phenanthrols. Exposure to the volatile organic compounds benzene, acrolein, crotonaldehyde, and ethylene oxide will be measured by quantitation ofthe urinary mercapturic acids S-phenylmercapturic acid, 3- hydroxypropylmercapturic acid, 4-hydroxybut-2-ylmercapturic acid, and 2-hydroxyethymercapturic acid, respectively. The measurements will be carried out on a total of 2450 urine samples, and the results will be used by all projects. All assays use mass spectrometry with appropriately labeled internal standards for detection and quantitation, and all have been analytically validated with respect to accuracy and precision. Personnel in this Core have years of experience in the quantitation of urinary metabolites of tobacco smoke constituents and were the first to develop many of the methods being used. This Core is critical for the proposed studies in the program project relating metabolic phenotypes, as measured here, to the results of genome wide association studies and for determining differences in mechanisms of tobacco carcinogenesis in ethnic groups at different risk for lung cancer.